Mosquito-transmitted parasitic diseases are among the major causes of mortality and morbidity in the world. Recent dramatic increases in the incidence of mosquito-borne diseases underscore the need for new approaches to insect control based on mosquito specific agents. The discovery of such mosquito-specific agents depends on basicresearch on the biology of mosquitoes. However, there is a serious deficiency in our understanding of nearly all aspects of mosquito biology. Juvenile Hormone (JH) is amajor hormonal regulator in insects. In adult female mosquito JH signals that ecdysis to the adult stage is complete and reproductive processes should begin, inducing simultaneous changes in the expression of many genes in ovarian, fat body and midgut tissues. We have shown that JH plays an essential role in the transcriptionalactivation of the early trypsin gene in the Aedes aegypti midgut. The early trypsin is aremarkable"molecular marker," its expression is dramatically modified after feeding, and it is affected by both hormones and nutrients. We propose to use the expression of theearly trypsin gene as a paradigm for the nutritional regulation of JET levels. The ultimate goal of this project is to understand how changes in the nutritional status are assessed, and this information is transduced to coordinate post-feeding physiology. In this proposal, we are focusing on thenutritional regulation of JH levels. Our hypothesis is that the midgut can detect the nutritional status after feeding, and regulates the JR levels by affecting the activity of the corpora allata (CA). This regulation could be mediated directly or indirectly bymidgut peptides synthesized by the endocrine cells and released into the hemolymph. We have established an in vitro radiochemical assay to measure the synthesis of JH by the CA, using this assay we have shown that midgut peptide extracts stimulate thesynthesis of JET by the CA, and also that an Aedes aegyptiallatotropin stimulatesthesynthesis of JET by the CA. In order to define how JR levels are regulated after a blood meal, the following specific aims are proposed: (1) To investigate the role of the Aedes aegypti allatotropin and allatostatins on the regulation of CA activity in vitro, (2) To identify identify the peptide(s) responsible for the midgut allato-regulatory activity and (3) To investigate the physiological role of allato-regulatory peptides "in vivo."